Comparison of simple Eudragit microparticles loaded with prednisolone and Eudragit-coated chitosan-succinyl-prednisolone conjugate microparticles: Part I. Particle characteristics and in vitro evaluation as a colonic delivery system

Objective: Simple Eudragit microparticles loaded with prednisolone and chitosan-succinyl-prednisolone conjugate microparticles coated with Eudragit were prepared and characterized in vitro in order to obtain their basic features as a colonic delivery system.

Materials and methods: Both types of microparticles were prepared by the emulsification-solvent evaporation modified somewhat from the previous one. Their particle size, shape and their drug content were investigated, and in vitro release profiles were examined using JP-15 1st fluid (pH 1.2), JP-15 2nd fluid (pH 6.8) and PBS (pH 7.4) as release media. Furthermore, the regeneration of conjugate microparticles from Eudragit-coated microparticles was investigated under the same incubation conditions.

Results: Simple Eudragit S100 (EuS) microparticles (ES-M) were almost spherical, ca. 1.2 μm diameter, and PD content ca. 3.7% (w/w). Conjugate microparticles (CS-M1) and EuS-coated conjugate microparticles (CS-M1/S) had particle sizes of ca. 2.8 and 15.3 μm, respectively, and PD contents of 5.4 and 2.1% (w/w), respectively. ES-M exhibited suppressed release at pH 1.2, gradual release at pH 6.8 and rapid release at pH 7.4. CS-M1 showed no release at pH 1.2, and very slow release at pH 6.8 and 7.4. CS-M1 regenerated poorly from CS-M1/S at pH 6.8.

Conclusions: Simple Eudragit micrparticles and Eudragit-caoted conjugate microparticles, prepared by the present methods, were found in vitro to be possibly useful as the delivery systems of PD to the lower intestine, although there were differences in their release rate and morphological features.     

Preparation and in vitro evaluation of chitosan microspheres containing prednisolone: comparison of simple and conjugate microspheres

The purpose of the present study was to obtain a novel microparticulate formulation of prednisolone, which was adequate for the treatment of inflammatory bowel disease (IBD). The formulations prepared were evaluated in vitro. Two types of chitosan microspheres containing prednisolone, named Ch-Pred and Ch-SP-MS, were prepared by an emulsification-solvent evaporation method using a chitosan-prednisolone mixture and a chitosan-succinyl-prednisolone conjugate (Ch-SP), respectively. Ch-Pred and Ch-SP-MS were obtained in almost spherical shape. Ch-Pred showed a relatively high drug content of 13.2% (w/w), but the particle size was distributed from 10 to 45 µm, and a large initial burst release of approximately 60% was observed. On the other hand, although Ch-SP-MS exhibited a fairly low drug content of 3.5% (w/w), their particle size ranged from several hundred nanometers to 20 µm, with the mean diameter of 5 µm, and a gradual drug release profile was achieved. These characteristics on particle size and in vitro release suggested that Ch-SP-MS should have good potential as a microparticulate system for the treatment of IBD.     

Preparation and in vitro/in vivo evaluation of gliclazide loaded Eudragit nanoparticles as a sustained release carriers

The aim of this study was to formulate and optimize gliclazide-loaded Eudragit nanoparticles (Eudragit L100 and Eudragit RS) as a sustained release carrier with enhanced efficacy. Eudragit L 100 nanoparticles (ELNP) were prepared by controlled precipitation method whereas Eudragit RSPO nanoparticles (ERSNP) were prepared by solvent evaporation method. The influence of various formulation factors (stirring speed, drug:polymer ratio, homogenization, and addition of surfactants) on particle size, drug loading, and encapsulation efficiency were investigated. The developed Eudragit nanoparticles (L100 and RS) showed high drug loading and encapsulation efficiencies with nanosize. Mean particle size altered by changing the drug:polymer ratio and stirring speed. Addition of surfactants showed a promise to increase drug loading, encapsulation efficiency, and decreased particle size of ELNP as well as ERSNP. Dissolution study revealed sustained release of gliclazide from Eudragit L100 as well as Eudragit RSPO NP. SEM study revealed spherical morphology of the developed Eudragit (L100 and RS) NP. FT-IR and DSC studies showed no interaction of gliclazide with polymers. Stability studies revealed that the gliclazide-loaded nanoparticles were stable at the end of 6 months. Developed Eudragit NPs revealed a decreased t_min (ELNP), and enhanced bioavailability and sustained activity (ELNP and ERSNP) and hence superior activity as compared to plain gliclazide in streptozotocin induced diabetic rat model and glucose-loaded diabetic rat model. The developed Eudragit (L100 and RSPO) NP could reduce dose frequency, decrease side effects, and improve patient compliance.     

Eudragit coating of chitosan-prednisolone conjugate microspheres and in vitro evaluation of coated microspheres

Chitosan-prednisolone conjugate microspheres (Ch-SP-MS) were prepared, and Eudragit coating was applied in order to efficiently deliver the microspheres and drug to the intestinal disease sites. The Eudragit L100-coated microspheres (Ch-SP-MS/EuL100) were examined for particle characteristics and the release of drug and Ch-SP-MS in different pH media at 37°C. Ch-SP-MS were spherical, with a mean size of 4.5 μm and prednisolone content of 3.3% (w/w). Ch-SP-MS/EuL100 were fairly spherical, with a mean size of 22. 5 μm and drug content of 0.32% (w/w). At pH 1.2, the release extent was less than 5% even at 48 h, and Eudragit coating tended to suppress the release. In contrast, at pH 6.8 and 7.4, Ch-SP-MS/EuL100 tended to show somewhat faster drug release than Ch-SP-MS. Ch-SP-MS/EuL100 displayed a release extent of 23 and 27% at pH 6.8 and 7.4, respectively. Ch-SP-MS aggregated at pH 1.2, but almost kept their initial size and shape at pH 6.8 and 7.4. Ch-SP-MS/EuL100 almost maintained their original shape and size at pH 1.2, and gradually released Ch-SP-MS at pH 6.8 and 7.4 due to dissolution of the Eudragit layer. Eudragit coating is suggested to be useful to efficiently deliver Ch-SP-MS to the intestinal disease sites.     

A chitosan lactate/poloxamer 407-based matrix containing Eudragit RS microparticles for vaginal delivery of econazole: design and in vitro evaluation

A matrix based on chitosan lactate and poloxamer 407 was evaluated as a delivery system for the vaginal administration of the antifungal drug econazole. The matrix was investigated both containing the pure drug and after introducing microparticles of Eudragit RS 100 containing econazole. Eudragit RS 100 microparticles were prepared using an emulsion-extraction method and dispersed in a solution containing chitosan lactate (2% w/w) and poloxamer 407 (1.7% w/w). The microparticles, obtained with a yield of 64% w/w and an encapsulation efficiency of 42% w/w, had a diameter of less than 2 μm and a drug loading of 13% w/w. The compressed matrices, characterized by DSC, swelling, erosion, release and mucoadhesion studies, had behaviours dependent on the relative amounts of the contained microparticles. The matrix without microparticles (MECN) showed zero-order release kinetics, with a maximum drug-release of 60% w/w, while those containing 50 or 75% w/w microparticles showed a diffusion controlled release up to 8 and 16 h, respectively, and a linear trend after those time intervals, caused by the erosion process, which allowed reaching a drug-release of approximately 100% w/w at 22 h. In in vitro experiments, the matrices were mucoadhesive and active in inhibiting the growth of Candida albicans 796.     

Transdermal delivery of propranolol using mixed grades of Eudragit: design and in vitro and in vivo evaluation

A matrix-dispersion-type transdermal drug delivery system of propranol was developed using different ratios of mixed polymeric grades of Eudragit. Formulations were evaluated for in vitro dissolution characteristics using a Cygnus' sandwich patch holder. Selected formulations followed zero-order release kinetics. In vivo evaluation was carried out on healthy human volunteers following a balanced incomplete block design (BIBD). In vitro dissolution rate constant k and pharmacokinetic parameters generated from plasma and urine were evaluated statistically. Statistically excellent correlation was found between percentages of drug absorbed from patch versus C_max, AUC_0-24, and AUC_0-∞. A highly significant difference was observed when C_max and AUC_0- generated from plasma and urine data were compared, but when k_e, t_1/2e, k_a, t_1/2awere compared, the difference was not significant. Urinary excretion data are suggested as a simpler alternative to blood-level data in studying the kinetics of absorption and deriving the absorption parameter.     

In vitro and in vivo anti-tumor effects of gemcitabine loaded with a new drug delivery system

In recent years, much attention has been given to liposomal formulation as an efficient drug loading system (DDS) in chemotherapy of cancer. In this study, the advantages of magnetic nanoparticles and Polyethylene Glyco (PEG) materials were considered to synthesize magnetic gemcitabine long-circulating liposomes (MGLL) and the potential of MGLL as a brand new delivery system was evaluated. MGLL was prepared using the reverse-phase evaporation method. In the optimized preparation, MGLL had an average diameter of 201 nm with a narrow size distribution measured by dynamic light scattering (DLS), which could be easily dispersed in ultrapure water under a stable state for 90 days. The encapsulation efficiency of gemcitabine in MGLL reached 87.2% as determined by HPLC. In vitro MTT assay showed that MGLL had significant cytotoxicity to MCF-7 cells compared with the conventional modalities. In vivo, the inhibition of tumor growth in MGLL group was more remarkable than that of other groups (P < 0.05). In conclusion, MGLL under optimized condition could be used as an effective carrier for tumor-targeted therapy.     

Development of isradipine loaded self-nano emulsifying powders for improved oral delivery: in vitro and in vivo evaluation

Isradipine (ISR) is a potent calcium channel blocker with low oral bioavailability due to low aqueous solubility, extensive first-pass metabolism and P-glycoprotein (P-gp)-mediated efflux transport. In the present investigation, an attempt was made to develop isradipine-loaded self-nano emulsifying powders (SNEP) for improved oral delivery. The liquid self-nano emulsifying formulations (L-SNEF/SNEF) of isradipine were developed using vehicles with highest drug solubility, i.e. Labrafil® M 2125 CS as oil phase, Capmul® MCM L8 and Cremophor® EL as surfactant/co-surfactant mixture. The developed formulations revealed desirable characteristics of self-emulsifying system such as nano-size globules ranging from 32.7 to 40.2?nm, rapid emulsification (around 60?s), thermodynamic stability and robustness to dilution. The optimized stable self-nano emulsifying formulation (SNEF₂) was transformed into SNEP using Neusilin US2 (SNEP_N) as adsorbent inert carrier, which exhibited similar characteristics of liquid SNEF. The solid state characterization of SNEP_N by Fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction and scanning electron microscopic studies shown transformation of crystalline drug into amorphous form or molecular state without any chemical interaction. The in vitro dissolution of SNEP_N compared to pure drug was indicated by 18-fold increased drug release within 5?min. In vivo pharmacokinetic studies in Wistar rats showed significant improvement of oral bioavailability of isradipine from SNEP_N with 3- and 2.5-fold increments in peak drug concentration (C_max), area under curve (AUC_0–∞) compared to pure isradipine. In conclusion, these results signify the improved oral delivery of isradipine from developed SNEP.     

Preparation and in vitro evaluation of pH, time-based and enzyme-degradable pellets for colonic drug delivery

The preparation of pH-dependent, time-based and enzyme degradable pellets was investigated for use as an oral colonic drug delivery system. It was expected that drug would be released immediately once the pellets reached the colon. The pellets were prepared using extrusion-spheronizing equipment and subsequently coated with three layers of three functional polymers by an air-suspension technique. The core consisted of 5-aminosalicylic acid (5-ASA) as a model drug, CaP as an enzyme-degradable material and microcrystalline cellulose (MCC) as an additive. As far as the three coated layers were concerned, the outer layer was coated with Eudragit L30D-55 for protection against gastrointestinal juices, the intermediate layer was coated with ethylcellulose (EC) to inhibit drug release during passage through the small intestine, and the inner film was coated with pectin for swelling and enzyme-degradation, which required a 30, 10, and 12% weight gain, respectively. Several micromeritic properties of the core pellets, including particle size distribution, particle size, degree of circularity, and friability, were evaluated to investigate the effects of the formulations of the cores and preparation conditions. Also, dissolution testing of the cores showed that the presence of calcium pectinate (CaP) markedly increased the drug release rate from the cores, as determined by scanning electron microscopy (SEM). In-vitro release studies indicated that the coated pellets completely protected the drug release in 0.1 mol/L HCl, while the drug release was delayed for 3-4 hr in pH 6.8 PBS. A synergistic effect of enzyme dependence for the coated pellets was seen following removal of the coated layer and during contact with colonic enzymes. Consequently, it was possible to achieve colon-specific drug delivery using this triple-dependence system.     

Acrylic resins as rate-controlling membranes in novel formulation of a nine-day 17beta-estradiol transdermal delivery system: in vitro and release modifier effect evaluation.

The feasibility of transdermal controlled delivery system of 17beta-estradiol was investigated by conducting in vitro release studies. Several new 17beta-estradiol unilaminate adhesive devices capable of releasing 17beta-estradiol in a controlled fashion over a 24-h, 36-h, 96-h, 104-h, 168-h, and 216-h period have been developed using acrylic resins (Eudragits E100, RSPO, and RLPO) as adhesive and rate-controlling polymers. The in vitro release profiles of 17beta-estradiol from various TDS unilaminate devices were characterized in a new developed dissolution tester vessel (total volume 200 ml), using a new paddle. The release of drug from different formulations was measured by a sensitive high-performance liquid chromatographic (HPLC) method. The release of drug from all prepared adhesive devices seems to obey zero-order kinetics (r > 0.98). The effect of two different plasticizers (acetyltriburyl citrate [ATBC] and triethyl citrate [TEC]) on the release patterns of 17beta-estradiol from TDS formulations was studied, and they were almost identical. The effect of two different release modifiers, propylene glycol (PG) and myristic acid (MA), on the release pattern of 17beta-estradiol from prepared unilaminate devices was evaluated. It was shown that the use of these release modifiers significantly increased the release of 17beta-estradiol from a TDS unilaminate patch. Furthermore, these data clearly demonstrated that the acrylic resins are suitable polymers for the preparation of 17beta-estradiol TDS adhesive devices.     

Development and in vitro evaluation of oxytetracycline‐loaded PMMA nanoparticles for oral delivery against anaplasmosis

Poly‐methyl methacrylate (PMMA) polymer with remarkable properties and merits are being preferred in various biomedical applications due to its biocompatibility, non‐toxicity and cost effectiveness. In this investigation, oxytetracycline‐loaded PMMA nanoparticles were prepared using nano‐precipitation method for the treatment of anaplasmosis. The prepared nanoparticles were characterised using dynamic light scattering (DLS), atomic force microscopy (AFM), differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. The mean average diameter of the nanoparticles ranged between 190–240 nm and zeta potential was found to be −19 mV. The drug loading capacity and entrapment efficiency of nanoparticles was found varied between 33.7–62.2% and 40.5–60.0%. The in vitro drug release profile exhibited a biphasic phenomenon indicating controlled drug release. The uptake of coumarin‐6(C‐6)‐loaded PMMA nanoparticles in Plasmodium falciparum (Pf 3D7) culture model was studied. The preferential uptake of C‐6‐loaded nanoparticles by the Plasmodium infected erythrocytes in comparison with the uninfected erythrocytes was observed under fluorescence microscopy. These findings suggest that oxytetracycline‐loaded PMMA nanoparticles were found to be an effective oral delivery vehicle and an alternative pharmaceutical formulation in anaplasmosis treatment, too.Inspec keywords: nanoparticles, nanomedicine, conducting polymers, microorganisms, cellular biophysics, toxicology, drug delivery systems, light scattering, atomic force microscopy, differential scanning calorimetry, Fourier transform infrared spectra, bloodOther keywords: in vitro evaluation, oxytetracycline‐loaded PMMA nanoparticles, anaplasmosis, polymethyl methacrylate polymer, biocompatibility, toxicity, oxytetracycline‐nanoparticles, nanoprecipitation method, dynamic light scattering, atomic force microscopy, AFM, differential scanning calorimetry, DSC, Fourier transform infrared spectroscopy, FTIR spectroscopy, zeta potential, drug loading capacity, entrapment efficiency, in vitro drug release profile, biphasic phenomenon, coumarin‐6(C‐6)‐loaded PMMA nanoparticles, plasmodium falciparum culture model, preferential uptake, plasmodium infected erythrocytes, fluorescence microscopy, oral delivery vehicle, anaplasmosis treatment, size 190 nm to 240 nm     

Bioactive borate glass scaffolds: in vitro and in vivo evaluation for use as a drug delivery system in the treatment of bone infection

The objective of this work was to evaluate borate bioactive glass scaffolds (with a composition in the system Na₂O–K₂O–MgO–CaO–B₂O₃–P₂O₅) as devices for the release of the drug Vancomycin in the treatment of bone infection. A solution of ammonium phosphate, with or without dissolved Vancomycin, was used to bond borate glass particles into the shape of pellets. The in vitro degradation of the pellets and their conversion to a hydroxyapatite-type material in a simulated body fluid (SBF) were investigated using weight loss measurements, chemical analysis, X-ray diffraction, and scanning electron microscopy. The results showed that greater than 90% of the glass in the scaffolds degraded within 1 week, to form poorly crystallized hydroxyapatite (HA). Pellets loaded with Vancomycin provided controlled release of the drug over 4 days. Vancomycin-loaded scaffolds were implanted into the right tibiae of rabbits infected with osteomyelitis. The efficacy of the treatment was assessed using microbiological examination and histology. The HA formed in the scaffolds in vivo, resulting from the conversion of the glass, served as structure to support the growth of new bone and blood vessels. The results in this work indicate that bioactive borate glass could provide a promising biodegradable and bioactive material for use as both a drug delivery system and a scaffold for bone repair.     

Damar Batu as a novel matrix former for the transdermal drug delivery: in vitro evaluation

Purpose: Damar Batu (DB) is a novel film-forming biomaterial obtained from Shorea species, evaluated in this study for its potential application in transdermal drug delivery system. Methods: DB was characterized initially in terms of acid value, softening point, molecular weight (M_w), polydispersity index (M_w/M_n), and glass transition temperature (T_g). Neat, plasticized films of DB were investigated for mechanical properties. The biomaterial was further investigated as a matrix-forming agent for transdermal drug delivery system. Developed matrix-type transdermal patches were evaluated for thickness and weight uniformity, folding endurance, drug content, in vitro drug release study, and skin permeation study. Results: On the basis of in vitro drug release and in vitro skin permeation performance, formulation containing DB/Eudragit RL100 (60 : 40) was found to be better than other formulations and was selected as the optimized formulation. IR analysis of physical mixture of drug and polymer and thin layer chromatography study exhibited compatibility between drug and polymer. Conclusion: From the outcome of this study, it can be concluded that applying suitable adhesive layer and backing membrane-developed DB/ERL100, transdermal patches can be of potential therapeutic use.     

In vitro and in vivo evaluation of a novel nonscrotal matrix-type transdermal delivery system of testosterone

A matrix-type testosterone (TS) transdermal delivery system for nonscrotal skin was developed with DuroTak 87-2510 as an adhesive polymer. When 3% dodecylamine was used in combination with 10% span 80, the in vitro rat permeation rate increased from 2.29 microg/cm2/hr to 6.51 microg/cm2/ hr as the TS loading dose increased from 2% to 6%. The maximum flux of experimental patch was about 14-fold higher than that of Testoderm. Release kinetics of TS from the patches was proportional to t1/2 following the Higuchi equation, and the release rate of TS increased as TS loading dose increased. Also, a good linear relationship between the skin permeation rate and the release rate was observed, which implies that the release rate is the rate-limiting process of the skin permeation. In vivo study showed that the plasma concentration of TS promptly increased and reached the peak level within 3-6 hours of application of the experimental patch. Area under the curve (AUC0 approximately 48) and Cmax also linearly increased in a dose-dependent manner up to 6% of TS. These results demonstrate the feasibility of developing a nonscrotal matrix-type transdermal delivery system of TS.     

Development and in vitro evaluation of a buccal drug delivery system based on preactivated thiolated pectin

The aim of this study was to evaluate the potential of preactivated thiolated pectin (Pec-Cys-MNA) for buccal drug delivery. Therefore, a gel formulation containing this novel polymer and the model drug lidocaine was prepared and investigated in vitro in terms of rheology, mucoadhesion, swelling behavior and drug release in comparison to formulations based on pectin (Pec) and thiolated pectin (Pec-Cys). Both pectin derivatives showed gel formation without addition of any other excipient due to self-crosslinking thiol groups. Under same conditions, pectin did not show gel formation. Viscosity of Pec-Cys-based formulation increased 92-fold and viscosity of Pec-Cys-MNA-based formulations by 4958-fold compared to pectin-based formulation. Gels did not dissolve in aqueous environment during several hours and were able to take up water. Mucoadhesion of pectin on buccal tissue could be improved significantly, value of total work of adhesion increased in the following rank order: Pec-Cys-MNA?>?Pec-Cys?>?Pec. The retention time of a model drug incorporated in gel formulations on buccal mucosa under continuous rinsing with phosphate-buffered saline was prolonged, after 1.5?h 3-fold higher amount of a model drug was to be found on tissue after application of Pec-Cys-MNA-based formulation compared to pectin-based and 2-fold compared to Pec-Cys-based formulation. The Pec-Cys-MNA-based gel showed a more sustained release of lidocaine than Pec-Cys-based gel, whereas pectin solution revealed an immediate release. According to these results, the self-crosslinking pectin-derivative is a promising tool for buccal application.     

Research evaluation. Part I: productivity and citedness of a German medical research institution

An evaluation exercise was performed involving 313 papers of research staff (66 persons) of the Deutsche Rheuma-Forschungszentrum (DRFZ) published in 2004?C2008. The records and citations to them were retrieved from the Web of Science (Thomson Reuters) in March 2010. The authors compared productivity and citedness of ??group leaders?? vs. ??regular scientists??, of ??male scientists?? vs. ??female scientists?? using citation-based indexes. It was found that ??group leaders?? are more prolific and cited more often than ??regular scientists??, the same is true considering ??male?? vs. ??female scientists??. The greatest contrast is observed between ??female leaders?? and ??female regular scientists??. The above mentioned differences are significant in indexes related to the number of papers, while values of indexes characterizing the quality of papers (average citation rate per paper and similar indexes) are not substantially different among the groups compared. The mean value of percentile rank index for all the 313 papers is 58.5, which is significantly higher than the global mean value of about 50. This fact is evidence of a higher citation status, on average, of the publications from the DRFZ.     

Microemulsion loaded hydrogel as a promising vehicle for dermal delivery of the antifungal sertaconazole: design,optimization and ex vivo evaluation

The purpose of the present study was to develop and optimize sertaconazole microemulsion-loaded hydrogel (STZ ME G) to enhance the dermal delivery and skin retention of the drug. Following screening of various oils for maximum drug solubility, 12 pseudoternary phase diagrams were constructed using oils (Peceol^®, Capryol^® 90), surfactants (Tween^® 80, Cremophor^® EL), a cosurfactant (Transcutol^® P) and water. A 2¹ × 3¹ × 2¹ × 3¹ full factorial design was employed to optimize a ME of desirable characteristics. The MEs were formulated by varying the oil type, oil concentration, surfactant type and surfactant: cosurfactant ratio. Optimized ME formulae F22 [5% Peceol^®, 55% Tween^® 80: Transcutol^® (1:2), 40% water] and F31 [5% Peceol^®, 55% Cremophor^® EL: Transcutol^® (1:2), 40% water] acquired mean droplet size of 75.21 and 8.68?nm, and zeta potential of 34.65 and 24.05?mV, respectively. Since F22 showed higher STZ skin retention during ex vivo studies (686.47?μg/cm²) than F31 (338.11?μg/cm²); hence it was incorporated in 0.5% Carbopol 934 gel to augment STZ skin retention capability. STZ ME G exhibited higher STZ skin retention (1086.1?μg/cm²) than the marketed product “Dermofix^® cream” (270.3?μg/cm²). The antimycotic activity against C.albicans revealed increased zones of inhibition for F22 and STZ ME G (35.75 and 30.5?mm, respectively) compared to Dermofix^® cream (26?mm). No histopathological changes were observed following topical application of STZ ME G on rats’ skin (n?=?9). Overall, the obtained results confirmed that the fabricated formulation could be a promising vehicle for the dermal delivery of STZ.     

Development of multiple-unit colon-targeted drug delivery system by using alginate: in vitro and in vivo evaluation

Drug delivery systems to the colon are being actively investigated. However, it is difficult to ensure that an oral preparation disintegrates specifically in the human colon. In this study, a pH- and enzyme-controlled, colon-targeted tablets (PECCTT) was established by using outer pH-coated layer and inner alginate-coated compression layer. The influence of the amount of alginate and enteric coat thickness on drug release had been investigated and the formulation that contained 30% alginate in compression layer and 13% weight gain in pH-coated layer was proved to protect the drug release from stomach and small intestine, the lag time was 7.04 ± 0.17 h, and 84.45 ± 1.3% of prednisone was released at 12 h. The results of drug release behaviors and SEM study indicated that drug release mechanism of PECCTT was corrosion. Hybrid scanner combining SPECT and CT was employed to monitor (99m)Tc-contained tablets in the human gastrointestinal tract (GIT) and to obtain the images of the disintegration process. The results showed that the tablet remained intact during its transit through the upper GIT, the anatomical site of disintegration was found to be the sigmoidal colon, and the disintegration of the tablet started at 8 h post-dose in the volunteer.     

Preparation and evaluation of poly(lactic-co-glycolic acid) microparticles as a carrier for pulmonary delivery of recombinant human interleukin-2: II. In vitro studies on aerodynamic properties of dry powder inhaler formulations

Objective: The aim of this study was the preparation and evaluation of dry powder formulations of recombinant human interleukin-2 (rhIL-2)-loaded microparticles to be administered to the lung by inhalation.

Methods: As indicated in our previous study, the microparticles were prepared by modified water-in-oil-in-water (w₁/o/w₃) double emulsion solvent extraction method using poly(lactic-co-glycolic acid) (PLGA) polymers. The dry powder formulations were prepared with blending of microparticles and mannitol as a coarse carrier. The actual aerodynamic characteristics of the microparticles alone and prepared mixtures with mannitol are evaluated by using the eight-stage Andersen cascade impactor.

Results: Due to the low tapped density of microparticles (<0.4?g/cm³), the theoretical aerodynamic diameter (MMADt) values were calculated (<5 μm) on the basis of the geometrical particle diameter and tapped density values. The lowest tapped density value (0.17?g/cm³) belongs to the cyclodextrin-containing formulation. According to the results obtained using the cascade impactor, the emitted doses for all microparticle formulations were found to be rather high and during the aerosolization for all the formulations except F3 and F5, >90% of the capsule content was determined to be released. However, the actual aerodynamic diameter (MMADa) values were seen to be higher than the MMADt values. The blending of the microparticles with mannitol allowed their aerodynamic diameters to decrease and their fine particle fraction values to increase.

Conclusion: The obtained results have shown that the mixing of rhIL-2-loaded microparticles with mannitol possess suitable aerodynamic characteristics to be administered to the lungs by inhalation.     

Development of interventional whole body hyperthermia system: Part I: Device fabrication and performance evaluation

The whole body hyperthermia (WBH) is being regarded as a very promising way capable of efficiently treating patient with tumors already disseminated throughout the human body. However, there is currently a strong lack of an easy to administrate, highly efficient and minimally invasive heating strategy. In this paper, aiming to tackle such a bottle neck issue, the interventional whole body hyperthermia (IWBH) system through directly heating the blood flow via minimally invasive heating needle was successfully developed for the first time. As the first part of the present companying research, this paper was dedicated to illustrate in detail the device construction, and to test its heating capability with a series of simulating experiments. Comprehensive evaluations demonstrated that the new device is highly efficient, easy to administrate and reliable in raising patient’s body core temperature. Specially, the physical simulation experiments performed in the current study present a new perspective on studying the behavior of the temperature response of the human body subjected to endovascular heating. The animal test will be reported in our another companying paper.